Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Complement activation and oxidative cell damage are hallmarks of delayed kidney graft function (DGF) due to ischemia-reperfusion injury (IRI). Endothelial progenitor cells (EPC) protect from IRI by paracrine mechanisms including the release of extracellular vesicles (EV), microparticles involved in intercellular communication through horizontal RNA transfer. The aim of this study is to evaluate the protective role of EPC EV in kidney IRI through the limitation of complement activation and oxidative stress.
EV released from bone marrow EPC size 60-130 nm and carry mRNA coding for the complement inhibitors Factor H, CD55 and CD59, the anti-oxidant transcription factor nrf2 and express pro-angiogenic microRNA including miR-126 and miR-296.
In an experimental model of kidney IRI, EV localized within peritubular capillaries and tubular cells exerting morphologic and functional protection from acute kidney injury (AKI) with a reduced expression of C5b9 and up-regulation of CD55, CD59, Factor H and nrf2.
In vitro, EPC EV reduced hypoxia- and complement-induced apoptosis/senescence of tubular cells (caspase activation, Klotho) and triggered angiogenesis of endothelial cells inhibiting their phenotype change due to mesenchymal transition (EndoMT). EV modulate in renal cells different pathways such as Akt, Erk and HO-1. The specific role of Factor H, DAF, CD59 or nrf2 mRNA transfer to injured renal cells was confirmed by using RNase-treated EV or EV released from EPC engineered to knock-down complement inhibitors or nrf2 by specific siRNA. The role of microRNA was studied by using EV released from EPC transfected with siRNA for Dicer, the intracellular enzyme essential for microRNA production.
EPC-derived EV induce a regenerative program in renal resident cells by delivering microRNA and mRNA able to inhibit complement activation and oxidative cell injury. These results suggest the potential use of EPC EV as therapeutic option to limit DGF in kidney transplantation.
CITATION INFORMATION: Cantaluppi V., Medica D., Dellepiane S., Merlotti G., Airoldi A., Quaglia M., Castellano G., Gesualdo L., Camussi G. Endothelial Progenitor Cell-Derived Extracellular Vesicles Inhibit Kidney Ischemia-Reperfusion Injury through the Transfer of Specific microRNA and mRNA Coding for the Complement Inhibitors CD55, CD59, Factor H and for the Transcription Factor NRF2: Relevance for Delayed Kidney Graft Function Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Cantaluppi V, Medica D, Dellepiane S, Merlotti G, Airoldi A, Quaglia M, Castellano G, Gesualdo L, Camussi G. Endothelial Progenitor Cell-Derived Extracellular Vesicles Inhibit Kidney Ischemia-Reperfusion Injury through the Transfer of Specific microRNA and mRNA Coding for the Complement Inhibitors CD55, CD59, Factor H and for the Transcription Factor NRF2: Relevance for Delayed Kidney Graft Function [abstract]. https://atcmeetingabstracts.com/abstract/endothelial-progenitor-cell-derived-extracellular-vesicles-inhibit-kidney-ischemia-reperfusion-injury-through-the-transfer-of-specific-microrna-and-mrna-coding-for-the-complement-inhibitors-cd55-cd59/. Accessed March 23, 2019.
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